Project Summary Current treatments for opioid dependence would benefit by the addition of a non-opioid based treatment medication. Recent pre-clinical studies have demonstrated the involvement of the NK1 rector in opioid reward and withdrawal. This study proposes to investigate a clinically available the NK1 antagonist, aprepitant, in opioid dependent patients. Based on the unique behavioral and pharmacological characteristics of opioid addiction, and what is known of the currently employed treatments, we propose that the therapeutic mechanism of any potential opioid addiction treatment medication must include the ability to reduce opioid withdrawal. This is of particular importance during treatment initiation (eg. detoxification). In addition, for longterm treatment and relapse prevention it is important to manage drug craving, to ameliorate the effects of stress, and inhibit the rewarding effects of opioids if patients do experience a slip. Therefore, we propose to study aprepitant in the clinical laboratory, using models of acute opioid reward, reinforcement and withdrawal, as well as stress- and cue-exposure responding.